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  • PKP-015 Pharmacogenetic study of the effect of polymorphisms in the trailr1/trail system on the response to treatment with rituximab in follicular lymphoma patients

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Pharmacokinetics and pharmacodynamics
PKP-015 Pharmacogenetic study of the effect of polymorphisms in the trailr1/trail system on the response to treatment with rituximab in follicular lymphoma patients
  1. MR Gutiérrez Cívicos1,
  2. I Español Morales2,
  3. P Conesa Zamora3,
  4. D Gutiérrez-Meca Maestre2,
  5. MH García Lagunar1,
  6. I Muñoz García1,
  7. R Guerrero Bautista1,
  8. E Ferris Villanueva1,
  9. A García Márquez1,
  10. M Martínez Penella1
  1. 1Hospital General Universitario Santa Lucia, Pharmacy, Cartagena, Spain
  2. 2Hospital General Universitario Santa Lucia, Hematology, Cartagena, Spain
  3. 3Hospital General Universitario Santa Lucia, Molecular Pathology and Pharmacogenetics, Cartagena, Spain

Abstract

Background The interindividual variability in drug response and toxicity is well known and may be related to genetic factors. TRAIL and TRAILR1 are proteins involved in the induction of apoptosis by the extrinsic pathway and may be implicated in the mechanism of action of the anti-CD20 agent, rituximab.

Purpose To assess the influence of the functional gene polymorphisms rs20576 TRAILR1 and rs12488654 TRAIL on response to treatment with rituximab in follicular lymphoma (FL) patients.

Material and methods FL patients treated with rituximab in combination with first line chemotherapy in a level 3 Hospital. The clinical response was assessed after the fourth cycle and treatment completed, response criteria used were proposed by the International Working Group [Complete Response (CR), Partial Response (PR), Stable Disease (SD), Relapsed Disease (RD), considered SD and RD for non-responders (NR)]. Genes polymorphisms were determined by allelic discrimination using fluorescence probes and a 7500F real time termocycler. Statistical analysis of the data was performed using the program Epidat 3.1 (p < 0.05 as statistically significant).

Results 40 patients were included (60% men). Average age: 58 ± 16 years. Pharmacogenetic study was performed to 31 patients at the fourth cycle and to 39 at the end of the treatment. Distribution for response/genotypes:

  • After fourth cycle: NR [AA = 1(100%)], PR [AA = 8(50%), CA = 8(50%)], CR [AA = 10(71.4%), CA = 4(28.6%)] (polymorphism rs20576); NR [GA = 1(100%)], PR [AA = 1(6.3%), GA = 5(31.3%), GG = 10(62.5%)], CR [AA = 1(7.1%), GA = 2(14.3%), GG = 11(78.6%)] (polymorphism rs12488654).

  • Treatment completed: NR [AA = 1(100%)], PR [AA = 4(57.1%), CA = 3(42.9%)], CR [AA = 17(54.8%), CA = 13(41.9%), CC = 1(3.2%)] (polymorphism rs20576); NR [GA = 1(100%)], PR [GA = 2(28.6%), GG = 5(71.4%)], CR [AA = 2(6.7%), GA = 7(23.3%), GG = 21(70%)] (polymorphism rs12488654).

There were no statistically significant differences between genotypes of polymorphisms (rs20576; rs12488654) and clinical response to rituximab after fourth cycle (p = 0.3503; p = 0.3930) and treatment completed (p = 0.9050; p = 0.4908).

Conclusion According to the results of our study, genes polymorphisms rs20576 TRAILR1 and rs12488654 TRAIL do not appear to influence the response to treatment with rituximab in FL.

References and/or acknowledgements Haematology Department.

No conflict of interest.

https://doi.org/10.1136/ejhpharm-2015-000639.330

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